T2D Treatment Guidelines

What is preferred initial T2D therapy in patients with ASCVD, heart failure, or CKD?

GLP-1 agonist or SGLT2 inhibitor with proven cardiorenal benefit

When should 2 medications be started at baseline for T2D?

if A1C 8.5–10%

When should insulin be considered as initial therapy for T2D?

if A1C >10%, BG ≥300 mg/dL, catabolic symptoms (e.g., weight loss), or hyperglycemic symptoms (e.g., polyuria, polydipsia)

Outside of severe hyperglycemia, what injectable therapy is preferred over insulin in T2D?

GLP-1 agonist or dual GIP/GLP-1 agonist

What factors guide add-on therapy when A1C remains above goal in a type 2 diabetic?

Glycemic efficacy, weight effects, cost, hypoglycemia risk, etc

Which T2D medication combinations should be avoided and why?

DPP-4 inhibitor + GLP-1 agonist due to overlapping mechanisms;

sulfonylurea + insulin due to high hypoglycemia risk

What is the preferred treatment pathway for T2D with ASCVD or high ASCVD risk?

GLP-1 agonist or SGLT2 inhibitor with benefit → if A1C remains above goal, add the other class or a TZD

How is high ASCVD risk defined in the T2D treatment algorithm?

Age ≥55 years + ≥2 additional risk factors such as obesity, hypertension, smoking, dyslipidemia, or albuminuria

What is the preferred treatment for T2D with heart failure?

SGLT2 inhibitor with proven benefit

What additional therapy may benefit symptomatic HFpEF with obesity?

GIP/GLP-1 agonist or GLP-1 agonist with benefit

What is the preferred treatment pathway for T2D with CKD?

SGLT2 inhibitor or GLP-1 agonist with benefit → if A1C remains above goal, add the other class

How does kidney function affect SGLT2 inhibitor use in CKD?

Recommended if eGFR ≥20 mL/min/1.73 m²; glycemic efficacy decreases at eGFR <45; continue until dialysis or transplant

Which T2D drugs have very high or high BG-lowering efficacy?

GLP-1 agonists, tirzepatide, insulin, metformin, SGLT2 inhibitors, sulfonylureas, and TZDs

Which T2D drug class has intermediate BG-lowering efficacy?

DPP-4 inhibitors

Which T2D drugs are most effective for weight loss?

Very high/high: tirzepatide, semaglutide, dulaglutide, liraglutide; intermediate: other GLP-1 agonists and SGLT2 inhibitors; neutral: DPP-4 inhibitors and metformin

Which GLP-1 and SGLT2 drugs have demonstrated cardiovascular or renal benefits?

GLP-1: dulaglutide, liraglutide, semaglutide; SGLT2: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin

Which T2D medications are preferred in patients with MASH or MASLD?

GLP-1 agonist, GIP/GLP-1 agonist, or TZD